Inhibition of electrogenic Na(+)-pumping in isolated atrial tissue from patients treated with digoxin.
The effect on the cardiac sarcolemmal Na+,K(+)-pump of therapeutic concentrations of cardiac glycosides administered long-term to humans in a clinical setting is uncertain. We therefore examined Na+,K(+)-pump activity in atrial tissue from two groups of patients undergoing cardiac surgery. Fourteen patients received digoxin long-term until the time of surgery and 12 "controls" never received digoxin. The hyperpolarization produced by the electrogenic Na+,K(+)-pump in response to an increase in intracellular Na+ activity was utilized to evaluate Na+,K+)-pump activity. After excision from the patients, specimens of atrial tissue were Na(+)-loaded by cooling to 2-3 degrees C for 1 hr. They were then warmed to 30 degrees C in Tyrode's solution containing 20 mM K+. After warming the resting membrane potential of the tissues from both groups transiently hyperpolarized to levels more negative than the equilibrium potential for K+ (= approximately -50 mV in 20 mM K+) indicating that the hyperpolarization was the consequence of electrogenic Na(+(-pumping. The maximal hyperpolarization of the resting potential in tissue from patients receiving digoxin long-term (-58.4 +/- 1.9 mV, mean +/- S.D.) was significantly (P less than .01) less negative than that in tissue from patients in the control group (-69.9 +/- 2.2 mV). These data support the hypothesis that digoxin, administered therapeutically in the clinical setting, can inhibit the Na(+)-pump in human heart, and that during long-term administration of digoxin the inhibition can be sustained.
Rasmussen
H H
HH
Reingold ECC Center, Department of Medicine, Northwestern University, Chicago, Illinois.
Okita
G T
GT
Hartz
R S
RS
ten Eick
R E
RE
D004077:Digoxin / Q000494:pharmacology*; D006321:Heart / Q000187:drug effects*; D006801:Humans; D066298:In Vitro Techniques; D009206:Myocardium / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D012964:Sodium / Q000378:metabolism*; D015854:Up-Regulation
D004077:Digoxin; D012964:Sodium; D011188:Potassium